title: Gender-dependent effects of gonadectomy on lung carcinogenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female and male A/J mice.
abstract: The present study was conducted to investigate the effects of gonadectomy on lung carcinogenesis in female and male mice, and to determine an association between sex hormone and lung carcinogenesis. Female and male A/J mice were divided into gonadectomized and unoperated control groups and all animals were treated intraperitoneally with 1 or 2 injections of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) at the dose of 2 mg/mouse. The mice were sacrificed 18 or 56 weeks after surgery. Serum levels of estradiol in females and testosterone in males were confirmed to be decreased by gonadectomy. Lung white nodules were detected in all mice of all groups. In the control groups of 18- and 56-week studies, the multiplicities of lung nodules in females were significantly greater than in males. In males in the 56-week study, the multiplicity of macroscopical lung nodules, bronchiolo-alveolar hyperplasias, adenomas and tumors (adenomas and adenocarcinomas) showed significant increase with castration. In females in the 18-week study, the multiplicity of adenomas decreased significantly by ovariectomy. Based on the results of the present study, female A/J mice were confirmed to be more susceptible to NNK-induced lung carcinogenesis than males. Furthermore, it was suggested that the process is inhibited by testosterone and accelerated by estradiol. These findings indicate the possibility that sex hormones play important roles in determining sex differences in lung carcinogenesis in the A/J mice initiated by NNK.
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Ninomiya
authors.forename: Masanao
authors.initials: M
authors.lastname: Yokohira
authors.forename: Sosuke
authors.initials: S
authors.lastname: Kishi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakano
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamakawa
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Inoue
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kuno
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imaida
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D000236:Adenoma / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D009376:Neoplasms, Hormone-Dependent / Q000097:blood / Q000235:genetics / Q000473:pathology; D009602:Nitrosamines / Q000633:toxicity*; D009919:Orchiectomy; D010052:Ovariectomy; D012727:Sex Characteristics; D013739:Testosterone / Q000097:blood
chemical_list: D009602:Nitrosamines; D013739:Testosterone; D004958:Estradiol; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone